The present invention relates to new 3-mercapto-alkanols enriched in particular stereoisomers, to flavoring compositions containing and to food or beverage products flavored with at least one of these enriched compounds, and to a method for the preparation of both diastereoisomers of 3-mercapto-2-methyl-butan-1-ol.
In the food and beverage industry flavors play a critical role in the appreciation of food and beverage products. Hereafter the term flavor shall also include aroma and/or taste and in the following context all these terms are used interchangeably.
Several mercapto-alkan-1-ol compounds have been identified as flavorants in food products. Thus, 3-mercapto-hexan-1-ol has been identified in the yellow passion fruit (Passiflora edulis f. flavicarpa) (K. -H. Engel, R. Tressel, J. Agric. Food Chem. 1991, 39, 2249), in Sauvignon blanc wine (T. Tominaga, A. Furrer, R. Henry, D. Dubourdieu, Flavour Fragrance J. 1998, 13, 159; P. Werkhoff, M. Gxc3xcntert, G. Krammer, H. Sommer, J. Kaulen, J. Agric. Food Chem. 1998, 46, 1076), and in red Bordeaux wine (P. Bouchilloux, P. Darriet, R. Henry, V. Lavigne-Cruxc3xa8ge, D. Dubourdieu, J. Agric. Food Chem. 1998, 46, 3095), and is usually described as having passion fruit and grapefruit character.
3-mercapto-3-methyl-butan-1-ol has been found in roasted coffee (W. Holscher, O. G. Vitzthum, H. Steinhart, J. Agric. Food Chem. 1992, 40, 655) and in Sauvignon blanc wine (T. Tominaga, A. Furrer, R. Henry, D. Dubourdieu, Flavour Fragrance J. 1998, 13, 159). The flavor description by Holscher et al. is sweet, soup-like.
3-mercapto-2-methyl-propan-1-ol has been identified in red Bordeaux wine (P. Bouchilloux, P. Darriet, R. Henry, V. Lavigne-Cruxc3xa9ge, D. Dubourdieu, J. Agric. Food Chem. 1998, 46, 3095) and has been described as broth, sweat-like.
The German Offenlegungsschrift 2316456 describes xcex3-mercapto-alcohols and their formate and acetate esters as important odorants and flavorants that are useful for the preparation and modification of a broad range of flavor compositions. These compounds have been described as faint green, onion-like, sulfury and sweaty with a broad range of taste thresholds.
New 3-mercapto-alkan-1-ols for use as flavor ingredients and/or as flavor enhancers are provided.
The invention is directed to new 3-mercapto-alkanol compounds. One of these compounds is 3-mercapto-2-methyl-butan-1-ol (formula I) 
and stereoisomers of 3-mercapto-2-methyl-butan-1-ol, in which the compound is either enriched for the unlike isomer relative to the like isomer, or is enriched for the like isomer relative to the unlike isomer. The compounds may be enriched for the particular isomer at various ratios.
The invention is also directed to a 3-mercapto-2-methyl-butan-1-ol flavor composition enriched in the unlike isomer relative to the like isomer at ratios of  greater than 3:1,  greater than 4:1,  greater than 6:1,  greater than 10:1,  greater than 20:1, 30 greater than :1, or  greater than 40:1, or enriched in the like isomer relative to the unlike isomer at ratios of  greater than 10:1,  greater than 20:1,  greater than 30:1,  greater than 40:1,  greater than 50:1, or  greater than 100:1. The flavor composition may be enriched in the particular isomer. In one embodiment, the enrichment for unlike isomer relative to the like isomer is in the range of about 6:1 to about 50:1. In another embodiment, the enrichment for unlike isomer relative to the like isomer is in the range from  greater than 3:1 to about 50:1. In one embodiment, the enrichment for like isomer relative to the unlike isomer is in the range from about 30:1 to about 100:1. In another embodiment, the enrichment for like isomer relative to the unlike isomer is in the range from  greater than 10:1 to about 100:1.
The invention is also directed to a method of flavoring a product by adding to the product 3-mercapto-2-methyl-butan-1-ol (formula I) and stereoisomers of 3-mercapto-2-methyl-butan-1-ol, in which the compound is enriched in the unlike isomer relative to the like isomer, or enriched in the like isomer relative to the unlike isomer, in an amount effective to flavor the product. The product may be a food or beverage, and the compounds may be enriched in the unlike isomer relative to the like isomer at ratios of  greater than 3:1,  greater than 4:1,  greater than 6:1,  greater than 10:1,  greater than 20:1,  greater than 30:1, or  greater than 40:1, or in the range of  greater than 3:1 to about 50:1, or in the range of about 6:1 to about 50:1, or may be enriched in the like isomer relative to the unlike isomer at ratios of  greater than 10:1,  greater than 20:1,  greater than 30:1,  greater than 40:1,  greater than 50:1, or  greater than 100:1, or in the range of  greater than 10:1 to about 100:1, or in the range of about 30:1 to about 100:1.
The invention is also directed to a food or beverage product containing a flavor/aroma composition comprising a 3-mercapto-2-methyl-butan-1-ol enriched in the unlike isomer relative to the like isomer, or enriched in the like isomer relative to the unlike isomer.
Another of these compounds is 3-mercapto-3-methyl-hexan-1-ol (formula II) 
and stereoisomers of 3-mercapto-3-methyl-hexan-1-ol.
In one embodiment, the compound is a stereoisomer of 3-mercapto-2-methyl-butan-1-ol having a relative unlike (u) configuration (formula III) 
or the enantiomer of III. 
In an alternative embodiment the compound is a diastereomer of 3-mercapto-2-methyl-butan-1-ol having a relative like (l) configuration (formula IV) 
or the enantiomer of IV.
The above compounds may be used as flavorants in foods and/or beverages. The 3-mercapto-2-methyl-butan-1-ol and stereoisomer compounds provide cooked vegetable and meaty flavor/aroma notes to food products. The (S) isomer of 3-mercapto-3-methyl-hexan-1-ol enhances meaty notes, while the (R) isomer of 3-mercapto-3-methyl-hexan-1-ol enhances natural fruity character of exotic fruit flavors.
The invention is also directed to a flavor composition containing one or a combination of these compounds. In alternative embodiments, the flavor composition contains (rac)-3-mercapto-3-methyl-hexan-1-ol, (S)-3-mercapto-3-methyl-hexan-1-ol, or (R)-3-mercapto-3-methyl-hexan-1-ol. The compound in the flavor composition is at a concentration in the range of about 0.01 ppb to 50 ppm. The invention is also directed to a food or beverage product containing the above flavor compositions.
The invention is further directed to a method of flavoring a product, such as a food, beverage, oral hygiene product, pharmaceutical, or chewing gum, by adding one or a combination of the above compounds in an amount sufficient to flavor the product. The concentration of the compound may be in the range of about 0.01 ppb to 50 ppm.
The invention is still further directed to methods to synthesize 3-mercapto-2-methyl-butan-1-ol and stereoisomers, and 3-mercapto-3-methyl-hexan-1-ol and stereoisomers.
It has now been found that two new mercapto-alkanols, namely 3-mercapto-2-methyl-butan-1-ol of formula I 
and 3-mercapto-3-methyl-hexan-1-ol of formula II 
including all possible stereoisomers have very interesting flavor properties that are strongly dependent on the absolute and relative configurations of the compounds.
Especially interesting are the flavor properties of the two diastereoisomeric forms of 3-mercapto-2-methyl-butan-1-ol. As known to one skilled in the art, it will be appreciated that (u)-3-mercapto-2-methyl-butan-1-ol of formula III includes both (S)(R) and (R)(S) enantiomers (formulas IIIa and IIIb, respectively). 
As known to one skilled in the art, it will also be appreciated that (l)-3-mercapto-2-methyl-butan-1-ol of formula IV includes both (R)(R) and (S)(S) enantiomers (formulas IVa and IVb, respectively). 
which is depicted generally as 
It has been found that the (u)-3-mercapto-2-methyl-butan-1-ol enantiomers exhibit a strong onion-like note, with a surprisingly extreme low odor threshold value of 4 pg/l air. Due to this extremely strong aroma, (u)-3-mercapto-2-methyl-butan-1-ol of formula III is a valuable flavor ingredient, and even at concentrations of down to 0.01 ppb in water, the flavor of these compounds can be recognized. It has been found that the enantiomers of formula III are useful to enhance the meaty, boiled meat character of a food product, especially meat products, at concentrations of 0.1 ppb to 1 ppb and to impart cooked vegetable and meaty notes to food products, especially soup products, at concentrations from 1 ppb to 100 ppb.
It has been further found that the (l)-3-mercapto-2-methyl-butan-1-ol enantiomers of formula IV exhibit a herbaceous, onion-like, leeky and gassy character with a far higher threshold value of about 400 pg/l air as compared to the enantiomers of formula III. Surprisingly, it has been found that this compound is useful to enhance the typical natural, fruity character of exotic fruits at concentrations of 10 ppb to 50 ppm in a food product, preferably at concentrations in the range of 100 ppb to 5 ppm. The more enriched for the (l)-3-mercapto-2-methyl-butan-1-ol enantiometers, either (R)(R) or (S)(S), the less of an onion-like note is imparted. Thus, compositions enriched in (l)-3-mercapto-2-methyl-butan-1-ol at a ratio of, e.g.,  greater than 50:1 or  greater than 100:1 relative to (u)-3-mercapto-2-methyl-butanol-1-ol have less of an onion-like note. The same compositions enriched at lower ratios (e.g.,  greater than 10:1,  greater than 20:1 to about 50:1) have more of an onion-like note. These selective enrichments may be used to alter, augment, select, modify, etc., one or more particular flavor/taste/odor properties of the composition and/or the product containing the composition.
Compounds enriched in a particular diastereoisomer, and compositions containing these enriched compounds, are disclosed. The compounds of formulas III and IV are not limited to any particular isomer; all possible enantiomers and all mixtures are thus included within the scope of the invention. The use of these compounds to flavor food and beverage products, and the food and beverage products containing these enriched compounds, are also disclosed. The ratio of the unlike:like configuration in the enriched compositions may be in the range of  greater than 3:1,  greater than 4:1,  greater than 6:1,  greater than 10:1,  greater than 20:1,  greater than 30:1,  greater than 40:1 or to about 50:1. In embodiments, enrichment for the unlike configuration may be in the range between  greater than 3:1 to about 50:1, or may be in the range between about 6:1 and about 50:1. The ratio of the like:unlike configuration in the enriched compositions may be in the range of  greater than 10:1,  greater than 20:1,  greater than 30:1,  greater than 40:1,  greater than 50:1, or  greater than 100:1. In embodiments, enrichment for the like configuration may be in the range between  greater than 10:1 to about 100:1, or may be in the range between about 30:1 and about 100:1. That is, regardless of the total amount of 3-mercapto-2-methyl-butan-1-ol in the composition, the amount of one or the other diastereoisomer will be enriched relative to the other. Such enrichment imparts desirable flavor properties of products, such as food or beverage products.
It has also been found that the two enantiomers of 3-mercapto-3-methyl-hexan-1-ol have quite different olfactory properties, the (S)-isomer exhibits herbaceous, agrestic and green notes whereas the (R)-isomer can be described as grapefruit/passion fruit, black currant and onion-like. Both enantiomers exhibit an extremely strong aroma, even at concentrations of down to 0.1 ppb in water, and are therefore valuable flavor ingredients. The (S)-3-mercapto-3-methyl-hexan-1-ol is useful to enhance the flavor properties of food products, especially the meaty, boiled meat character of meat products the cooked vegetable and meaty notes of soup products. The amount of flavorant needed to impart these flavor characteristics depends on the food product to be flavored and is known to the person skilled in the art. Usually the concentrations range from 0.1 ppb to 1 ppm, preferably from 1 ppb to 100 ppb. The (R)-3-mercapto-3-methyl-hexan-1-ol is useful to enhance the typical natural, fruity character of exotic fruit flavors at concentrations of 10 ppb to 50 ppm in a food product, preferably at concentrations in the range of 100 ppb to 5 ppm.
Depending on the desired flavor properties of the finished food or beverage product, 3-mercapto-3-methyl-hexan-1-ol can be used in enantiomerically pure forms or as mixtures thereof.
The 3-mercapto-alkanols of the present invention are useful for flavoring various products such as foods, beverages, chewing gums, oral hygiene products, and pharmaceuticals, but are especially favored for flavoring foods and beverages. The 3-mercapto-alkan-1-ols according to the present invention can be added directly to the product or as flavor compositions comprising usual additives that are well known to a person of skill in the art. The 3-mercapto-alkan-1-ols according to the present invention can also be used in flavoring compositions to enhance or modify existing flavors in order to provide a specific flavor impression. They may then be incorporated into the flavoring compositions exclusively or in combination with further flavor ingredients such as esters, aldehydes, ketones, alcohols, lactones, heterocycles as e.g. furans, pyridines, pyrazines, and other sulfur compounds as e.g. thiols, sulfides, disulfides and the like. As is known to one of skill in the art, these components can be combined in proportions normally used for flavoring preparation.
It may be desirable to prepare the inventive flavoring compositions by using carrier materials, e.g. gum arabic or maltodextrin, or solvents, e.g. ethanol, propyleneglycol, water or triacetin yielding, inter alia, emulsions. By using carrier materials or solvents, the desired physical form of the flavoring composition can be obtained. When the carrier materials form an emulsion, the flavoring composition may further contain emulsifiers such as mono- and diglycerides of fatty acids and the like. The inventive flavoring compositions may be used in spray-dried, liquid, encapsulated, emulsified, or other forms.
The 3-mercapto-alkan-1-ols of the present invention may be used solely or in combination with other flavor ingredients known by those skilled in the art. Thus, a flavor composition may contain one or more of the compounds according to the invention. The total content of one or more of these compounds is preferably in the range of 0.01 ppb to 50 ppm, preferably in the range of 1 ppb to 5 ppm, depending on the product to be flavored.
The invention also provides a procedure for the stereospecific synthesis of the two diastereoisomeric forms of 3-mercapto-2-methyl-butan-1-ol of formula I, namely (u)-3-mercapto-2-methyl-butan-1-ol of formula III and (l)-3-mercapto-2-methyl-butan-1-ol of formula IV. The procedure for the preparation of (u)-3-mercapto-2-methyl-butan-1-ol comprises the condensation of benzyl mercaptan with angelic acid methyl ester, the reduction of the formed ester with lithium aluminum hydride and subsequent debenzylation with sodium in liquid ammonia. Using this procedure (u)-3-mercapto-2-methyl-butan-1-ol is obtained with a diastereoisomeric purity of  greater than 6:1. The isomerically enriched product can be used as such as flavorant to enhance the flavor properties of a food product, or it can be purified by chromatography to get diastereomerically pure (u)-3-mercapto-2-methyl-butan-1-ol, to be rel. configuration: unlike used as flavorant as described infra.
The procedure for the preparation of (l)-3-mercapto-2-methyl-butan-1-ol comprises the condensation of benzyl mercaptan with tiglic acid methyl ester, the reduction of the formed ester with lithium aluminum hydride and subsequent debenzylation with sodium in liquid ammonia. Using this procedure (l)-3-mercapto-2-methyl-butan-1-ol is obtained with a diastereoisomeric purity of  greater than 30:1. The isomerically enriched product can be used as such as flavorant to enhance the flavor properties of a food product, or it can be purified by chromatography to get diastereomerically pure (l)-3-mercapto-2-methyl-butan-1-ol, to be rel. configuration: like used as flavorant as described infra.